Vocal fold injury (due to surgical intervention, cancer, or abuse) leads to the formation of scar tissue that seriously comprises the quality of voice production and can seriously detract from the quality of life for the patient. The current project proposes to investigate an approach for recontruction of vocal fold tissue by utilizing a naturally occurring extracellular matrix scaffold derived from xenogeneic vocal fold tissue. Vocal fold tissue is subjected to extreme magnitudes and frequencies of deformation, and the default mechanism of healing in the vocal fold is the formation of scar tissue which leads to significant clinical problems and quality of life issues. Extracellular matrix (ECM) technology has been shown to be successful for treating a variety of tissue in a clinical setting. The hypothesis for this specific approach is that the specific composition and architecture of the ECM in the vocal fold will provide the most desireable set of biologic signals to guide the development of functionally and morphologically appropriate vocal fold tissue after injury. The scope of this research project will include detailed structural biomechanical analysis to determine how the composition and architecture of the vocal fold allow its highly specific function. Furthermore, one goal of the project is to specifically show how the changes in the tissue composition and architecture after injury lead to alterations in function. This will be accomplished through the development of relevant biomechanical tests that will provide the opportunity for rigorous evaluation of the proposed therapeutic approaches with relevance to the clinical setting. An experienced interdisciplinary team consisting of biomechanical engineers, tissue engineers, physicians, and pathologists has been assembled to conduct these studies. A timeline for completion of these studies and quantitative criteria for success are provided. PUBLIC HEALTH RELEVANCE: Vocal fold scarring is a frequent disorder that can occur as a result of surgical trauma, intubation, vocal abuse, radiation for cancer, and some systemic illnesses. As a result, patients experience reduced quality of voice production (i.e., hoarseness) that can lead to loss of employment, limited social interactions, and generally, a decrease in their quality of life. Treatment modalities must be developed that address the underlying problem of disruption of the native organization and composition of the vocal fold tissue.